Regulatory pathways that control development through temporally specified gene activation and repression mechanisms have been recognized as “epigenetic” (i.e. heritable changes not involving alterations in the primary DNA code). The beta-globin locus is a paradigm for epigenetic regulation of lineage- and developmentally-specific gene expression. The human beta-globin locus is composed of epsilon- (embryonic), G-gamma- and A-gamma-(fetal) and delta- and beta- (adult) globin genes, which are spatially arranged from 5′ to 3′ and developmentally expressed in the same order. A number of polypeptides involved in the epigenetic regulation of the beta-globin locus and their uses are described herein.